title: A new regulatory mechanism of NF-kappaB activation by I-kappaBbeta in cancer cells.
abstract: Transglutaminase 2 (TGase 2) catalyzes covalent isopeptide bond formation between glutamine and lysine residues. Recently, we reported that TGase 2 activates nuclear factor-kappa B (NF-kappaB) by depleting inhibitor of NF-kappaBalpha (I-kappaBalpha) levels via polymer formation. Furthermore, TGase 2 expression synergistically increases NF-kappaB activity with canonical pathway. The major I-kappaB proteins such as I-kappaBalpha and I-kappaBbeta resemble each other in both primary sequence and tertiary structure. However, I-kappaBbeta does not degrade fully, while I-kappaBalpha degrades immediately in response to most stimuli. We found that I-kappaBbeta does not contain any of the previously identified TGase 2 target sites. In this study, both an in vitro cross-linking assay and a TGase 2 transfection assay revealed that I-kappaBbeta is independent from TGase 2-mediated polymerization. Furthermore, increased I-kappaBbeta expression reversed NF-kappaB activation in cancer cells, compensating for the loss of I-kappaBalpha via TGase 2 polymerization.
authors.affiliation: Molecular Oncology Branch, Division of Basic and Applied Sciences, Research Institute, National Cancer Center, Ilsandong-Gu, Goyang, Gyeonggi-Do, Republic of Korea.
authors.forename: Jung Mo
authors.initials: JM
authors.lastname: Kim
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.forename: Chunkyu
authors.initials: C
authors.lastname: Ko
authors.forename: Dae-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Kang-Seo
authors.initials: KS
authors.lastname: Park
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016415:Sequence Alignment; D011503:Transglutaminases / Q000378:metabolism
chemical_list: C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins